Cancer stem cell gene variants are associated with tumor recurrence

Abstract

The disclosure provides compositions and methods for determining the likely tumor recurrence in cancer patients by screening CD44, CD166 and/or LGR5 polymorphism in samples isolated from the patient.

1 . A method for aiding in the determination of or determining whether a cancer patient is likely to experience a longer or shorter time to tumor recurrence, comprising screening a tissuc or cell sample isolated from the patient for at least one polymorphism of CD44 rs8193 C/T (SEQ ID NO: 53), ALCAM rs1157 G/A (SEQ ID NO: 54) or LGR5 rs rs17109924 T/C (SEP ID NO: 55), wherein the presence of one or more genotypes of:
 (a) (T/T or C/T) for CD44 rs8193 C/T (SEQ ID NO: 53);   (b) (A/A or G/A) for ALCAM rs1157 G/A (SEQ ID NO: 54); or   (c) (C/C or T/C) for LGR5 rs17109924 T/C (SEQ ID NO: 55);   determines that the patient is likely to experience a longer time to tumor recurrence, or the presence of none of genotypes (a)-(c) determines that the patient is likely to experience a shorter time to tumor recurrence.   
     
     
         2 . The method of  claim 1 , wherein the presence of one or more genotypes of:
 (a) (T/T or C/T) for CD44 rs8193 C/T (SEQ ID NO: 53);   (b) (A/A or G/4\ for ALCAM rs1157 G/A (SEQ ID NO: 54);   (c) (C/C or T/C) for LGR5 rs17109924 T/C (SEQ ID NO: 55);   determines that the patient is likely to experience a longer time to tumor recurrence.   
     
     
         3 . The method of  claim 1  or  2 , wherein a patient likely to experience a longer time to tumor recurrence is as compared to a patient suffering from a same cancer and having none of genotypes (a)-(c). 
     
     
         4 . The method of  claim 1 , wherein the presence of none of genotypes (a)-(c) determines that the patient is likely to experience a shorter time to tumor recurrence. 
     
     
         5 . The method of  claim 1 , wherein a patient likely to experience a shorter time to tumor recurrence is as compared to a patient suffering from a same cancer and having one or more genotypes of (a)-(c). 
     
     
         6 . The method of  claim 1 , wherein the patient suffers from one or more cancer selected from lung cancer, non-small cell lung cancer, breast cancer, head and neck cancer, ovarian cancer, colon cancer, Stage II or Stage III colon cancer, localized gastric cancer, gastric adenocarcinoma, rectal cancer, colorectal cancer, esophageal cancer, gastric cancer, liver cancer, bone cancer, spleen cancer, pancreatic cancer, or gallbladder cancer. 
     
     
         7 . The method of  claim 1 , wherein the patient suffers from one or more colorectal cancer. 
     
     
         8 . The method of  claim 7 , wherein the gastrointestinal cancer is colon cancer. 
     
     
         9 . The method of  claim 1 , wherein the patient is a Stage II or III colon cancer patient. 
     
     
         10 . The method of  claim 1 , wherein the sample comprises at least one of a tumor cell or tumor tissue, a normal cell or normal tissue, a normal cell or normal tissue adjacent to a tumor, a normal cell or normal tissue corresponding to the tumor tissue type, a blood cell, a peripheral blood lymphocyte, or combinations thereof. 
     
     
         11 . The method of  claim 1 , wherein the sample is at least one of a cell or tissue sample recently isolated from the patient, a fixed tissue, a frozen tissue, a biopsy tissue, a resection tissue, a microdissected tissue, or combinations thereof. 
     
     
         12 . The method of  claim 1 , wherein the screening is by a method comprising polymerase chain reaction analysis (PCR), sequencing analysis, restriction enzyme analysis, mismatch cleavage analysis, single strand conformation polymorphism analysis, denaturing gradient gel electrophoresis, selective oligonucleotide hybridization, selective PCR amplification, selective primer extension, oligonucleotide ligation assay, exonuclease-resistant nucleotide analysis, Genetic Bit Analysis, primer-guided nucleotide incorporation analysis PCR, PCR-restriction fragment length polymorphism (PCR- RFLP), direct DNA sequencing, whole genome sequencing, and/or microarray. 
     
     
         13 . The method of  claim 1 , wherein the patient is an animal patient. 
     
     
         14 . The method of  claim 13 , wherein the patient is of the group of a mammalian, a human, a simian, a murine, a bovine, an equine, a porcine, a feline, a canine, or an ovine patient. 
     
     
         15 . The method of  claim 14 , wherein the patient is a human patient. 
     
     
         16 . A kit for use in aiding in the determination of or determining whether a cancer patient is likely to experience a longer or shorter time to tumor recurrence, comprising suitable primers or probes or a microarray for screening a tissue or cell sample isolated from the patient for at least one polymorphism of CD44 rs8193 C/T (SEQ ID NO: 53), ALCAM rs1157 G/A (SEQ ID NO: 54) or LGR5 rs17109924 T/C (SEQ ID NO: 55), and instructions for use therein. 
     
     
         17 . A prognostic panel of primer or probes or a microarray comprising nucleic acids that identify the genotype in a patient sample for determining at least two polymorphisms of CD44 rs8193 C/T (SEQ ID NO: 53), ALCAM rs1157 G/A (SEQ ID NO: 54) or LGR5 rs17109924 T/C (SEQ ID NO: 55).